Biocatalysis

An Industrial Perspective

Gonzalo de Gonzalo, Pablo Domínguez de María

• Publisher: Royal Society of Chemistry
• Year: 2017
• eBook ISBN: 9781788012461
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

Implementing biocatalytic strategies in an industrial setting at a commercial scale is a challenging task, necessitating a balance between industrial need against economic viability. With invited contributions from small and large-scale chemical and pharmaceutical companies, this book bridges the gap between academia and industry. Contributors discuss current processes, types of biocatalysts and improvements, industrial motivation and key aspects to economically succeed. With its focus on industry related issues, this book will be a useful tool for future research by both practitioners and academics.

Part I

Context and Challenges for Industrial Biocatalysis

CHAPTER 1

An Appreciation of Biocatalysis in the Swiss Manufacturing Environment

REBECCA BULLER^*a, KATRIN HECHT^a, MARCO ANTONIO MIRATA,^b AND HANS-PETER MEYER,^c

^a Zurich University of Applied Sciences, School of Life Sciences and Facility Management, Institute of Chemistry and Biotechnology, Einsiedlerstrasse 31, 8820 Wädenswil, Switzerland;

^b Lonza AG, 3930 Visp, Switzerland;

^c HES-SO Valais-Wallis, Institute of Life Technologies, Route du Rawyl 64, 1950 Sion, Switzerland

* E-mail: [email protected]

1.1 Introduction

Relative to its size and population, Switzerland is the global number one in the field of large and small molecule pharmaceuticals. Despite (or perhaps due to) being a small country without a colonial history or noteworthy natural resources with the exception of water, a remarkable landscape, and the brains of its inhabitants, Switzerland is one of the biotechnology hotspots in Europe. Once the rural poorhouse, Switzerland became one of the first countries to be industrialized. Chocolate, watches and banks are the typical enumerations of someone asked about the economic activities of Switzerland. The pharmaceutical and chemical industries are usually not mentioned, although they have become a major economic driver and source of wealth.

As in England, the seed for industrialization was the textile industry, which led to two other key industries in Switzerland: the machine industry and the chemical industry. The machine industry was effectively triggered by the continental blockade by Napoleon I in the early 19th century, which forced the local ironmongers to develop and construct their own looms, as they were cut off from English machines and spare parts. Indirectly the food industry, as represented by Nestlé, also profited, as industrialization favored food products that responded to the shorter time the working class had available for household chores. As elsewhere, the dyes required for the textile industry brought about the industrialization of organic chemistry. The subsequent expansion of the production of dyes to organic chemicals, small molecule pharmaceuticals and ultimately biopharmaceuticals was straightforward due to strategic foresight, visionary entrepreneurs, the openness of Switzerland to foreign capital, and entrepreneurial immigrants. The banks founded at that time also played a key role in capitalizing this industrialization. Unlike in other countries,¹ these developments were not hampered by absolutist rulers who clung to the political and societal status quo up to the second half of the 19th century.

Today, the Swiss chemical industry has moved up the value chain from the production of basic chemicals to the manufacture of fine chemicals. For example, although Lonza still successfully operates a cracker in Switzerland, which was built in the 1960s, competition has increased substantially as classic oil-producing countries have started to install on-site chemical production complexes to keep the first part of the value chain in their own country. Consequently, the chemical and pharmaceutical industries have continuously refocused on core competencies and high-value products, resulting in an entirely new landscape, structures and companies between 1970 and today.² The Swiss chemical industry is heavily dependent on foreign trade as only ∼5% of the sales are in the home market while 95% of the industry's products are exported. Furthermore, most raw materials for chemical and pharmaceutical production in Switzerland have to be imported, over 80% of them from the EU. The chemical and pharmaceutical industry is now the country’s leading exporter,³ generating 4% of its gross domestic product and selling products to other countries valued at around CHF 79 billion annually (roughly 40% of total Swiss exports). About 90% of roughly 3000 products manufactured by the Swiss chemical industry are chemical specialties.⁴ The industry employs ∼65 000 people in Switzerland and over 355 000 globally.

Switzerland has been ranked the most innovative country for the sixth consecutive year by the Global Innovation Index.⁵ Roche and Novartis rank among the top ten companies with the largest R&D investments, alongside other industrial giants such as Microsoft, Samsung, Toyota and Amazon.⁶ The Swiss chemical industry is focused on life science and chemical specialties, and the world-wide sales of the top ten Swiss companies is split as follows: pharmaceuticals 63%, fine and specialty chemicals 13%, crop protection 9%, diagnostics 8% and vitamins, flavors and fragrances 7%. Since 1980, the pharmaceutical share of the total volume of chemicals exported has doubled. The landscape has changed considerably through restructuring, one of the most prominent events being the merger of Ciba and Geigy (the ‘marriage of elephants’) followed by the integration of Sandoz, forming the global player Novartis.

In addition, its education system is a driver of innovation in Switzerland. At the academic level the Swiss Federal Institutes of Technology in Zurich and Lausanne and other Swiss universities are recognized world-wide for their cutting-edge research while the combination of practical work in a company and vocational education at a technical college results in highly qualified operators and laboratory workers.

In summary, the contemporary key success factors that have led to the high international ranking and success of the chemical pharmaceutical companies in Switzerland are:

• capacity for innovation and a favorable environment for start-ups;
• availability of capital and fiscal management;
• the dual education system and availability of a highly-qualified workforce;
• willingness to adapt to changing environments and markets, and restructure accordingly;
• established collaboration between academic and industrial partners (CTI⁷ and BRIDGE⁸);
• social partnership and harmonious labor relations.

But how is biotechnology embedded in this larger historical industrial context, particularly in Switzerland but also globally? As in most countries, biotechnology has a long history in Switzerland due to its use in bread, alcohol and vinegar production. However, looking at these examples in a modern biotechnology context is like equating the invention of the wheel some seven thousand years ago with the production of the automobile. Early biotechnology was neither an important economic factor nor an engineering discipline, as it relied on empiricism.

Even in the first half of the 20th century only a few industrial biotech processes were implemented. The most prominent examples are lactic acid, citric acid and the acetone–butanol–ethanol (ABE) fermentation developed by Chaim Weizmann for the British in World War I. Later the production of penicillin by fermentation and the first biotransformation processes were introduced (vitamin C, steroids). The pharmaceutical company Roche pioneered this field when they acquired the Reichstein patent in the 1930s and implemented their first biocatalytic process for the production of vitamin C before World War II. The resulting product, Redoxon, turned into a highly profitable asset for the company (Figure 1.1), rewarding Roche for the risk they had taken. In 2003, Roche sold its vitamin division to DSM, which now operates under the name of DSM Nutritional Products AG.

Figure 1.1 On the left, a photograph of an early vitamin C preparation from Roche. On the right, Professor Tadeus Reichstein, who succeeded in synthesizing vitamin C in 1933. His synthetic process contained one biocatalytic step. Tadeus Reichstein was titular professor at the University of Basel at the time, and won the Nobel Prize in Physiology and Medicine in 1950. Courtesy of F. Hoffmann-La Roche AG.

What today is recognized as the ‘modern biotechnology’ of the 20th and 21st centuries was triggered by two important breakthroughs, (i) the realization of large scale sterile aerobic fermentation and (ii) the application of genetic engineering in manufacturing. The rapid development of bioinformatics is the third element pushing today’s biotechnology to new frontiers. During the second half of the 20th century the application of modern biotechnology grew rapidly from the first ...

Table of contents

• Cover
• Title
• Copyright
• Contents
• Preface
• Part I Context and Challenges for Industrial Biocatalysis
• Part II Biocatalysis: from Pharmaceuticals to Bulk Chemistry
• Part III Biocatalyst Optimization with Industrial Perspectives
• Part IV Emerging Industrial Biocatalysis
• Subject Index